The present invention relates generally to the storage of blood cell components. More specifically, the present invention relates to the storage of the red blood cell component of blood.
It is known to centrifuge collected blood to remove plasma and the buffy-coat layer. The residue is a mass of red cells that is substantially separated from the plasma referred to as "packed red cells." The separation of the red cells from the plasma is desirable for a number of reasons. By separating the red cells, it is possible to collect the plasma and use the plasma for separate therapeutic uses.
Additionally, it is desirable in many disease states to administer red blood cells in a purified or semipurified form, thereby avoiding to transfer to the recipient such constituents of blood as plasma and white cells, when these are unsuitable.
Accordingly, it is known to store packed red cells separately and apart from at least a substantial portion of plasma. These red cells are later administered to a patient during major surgery and the like.
Although it is desirable to separately store and utilize the red cell component of whole blood, it was discovered that, unless special precautions are taken, packed red cells do not survive as well as red cells that are stored in the presence of an increased amount of plasma. Accordingly, to promote the long term storage of packed red cells, it has been suggested to admix packed red cells with at least a small amount of blood plasma.
It is known to store packed red cells in a 100 ml of a protein-poor solution containing for each unit of packed red cells, 877 mg of sodium chloride, 16.9 mg of adenine, and 900 mg of glucose (SAG) to increase the storage life of the red cells. See, Hogman et al, New England Journal of Medicine, Dec. 21, 1978; 229 (25); 1377-82.
It has also been suggested to use mannitol as a reagent to improve the viability of stored blood cells and create a storage solution. See, U.S. Pat. No. 4,082,509. The patent discloses a storage solution which includes both glucose (in an amount of 990 mg/ml) and mannitol (in an amount of 500 mg/ml). The solution provides an improved viability of the packed red cells stored in contact therewith.
European Published Patent No. 0 044 864 discloses a storage solution that provides improved storage time. Pursuant to the solution disclosed, the concentration of glucose (or fructose) is increased and mannitol is added to a conventional SAG solution. In an embodiment, an aqueous red blood cell storage solution is provided that contains per 100 ml of solution, substantially from 1500 to 2500 mg of sugar comprising glucose and/or fructose; from 500 to 1500 mg of mannitol; from 20 to 30 mg of adenine; and from 500 to 1000 mg of sodium chloride.
One difficulty that is encountered with storage solutions is the sterilization of the solutions. Glucose is known to degrade under autoclaving (heat) sterilization conditions unless it is maintained in an acidic medium. If glucose is not in an acidic medium, when heated, glucose will carmelize.
In collecting blood, specifically red cells, it is known to add to the whole blood collected from the donor an anticoagulant. The anticoagulant typically includes citrate. After the anticoagulant is added to the whole blood, the blood can be separated into components, including plasma and red blood cells. An example of an anticoagulant is citrate phosphate dextrose (CPD). During the separation process of the whole blood, typically much of the citrate separates with the plasma, leaving the red blood cells with lower citrate levels when they are then mixed with a storage solution.
It is known to include in the anticoagulant a surplus of citrate in order to obtain good binding of ionized calcium which otherwise may initiate plasma coagulation at blood collection or blood storage. However, a disadvantage with this procedure is poor stability of Factor VIII and reduced yield of this factor in subsequent blood component preparation.
It is known that reduction of the concentration of citrate in the anticoagulant improves the stability of Factor VIII, provided conditions during collection are optimal. This is a way to improve the yield of Factor VIII in plasma, when separation of the blood into components has to be carried out after a delay of several hours. Reduction of citrate in the anticoagulant has the additional advantage, when the red cells are stored in an additive solution based on citrate, that the citrate load in a recipient of massive volumes of both red cells and plasma will not be disturbingly high.
There is therefore a need for an improved red blood cell storage solution.